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Jin Jiang, Ph.D.
Ph.D., Columbia University - 1992
Professor, Departments of Developmental Biology and Pharmacology
Eugene Mc Dermott Scholar in Biomedical Research, UT Southwestern

Cell Regulation
Genetics and Development

Office: (214) 645-5914 Fax: (214) 648-1960
Building NB, Room 5.604B
Email: Jin.Jiang@utsouthwestern.edu

Key words: signal transduction, pattern formation and growth control, tumor suppressor gene, developmental genetics

Cell-cell communication (or induction) is a fundamental and prevalent mechanism that controls cell growth, cell fate determination and pattern formation of multicellular organisms. We are studying the nature of inductive signals, how inductive signals are generated and interpreted by cells, and how misregulation of cell signaling may cause diseases such as cancers.

Induction is often mediated by conserved signaling pathways, such as Hedgehog (Hh) and Wingless (Wg)/Wnt pathways. Mutations in genes of Hh and Wg/Wnt pathways have been linked to several types of cancers including basal cell carcinomas, the most common cancer afflicting some 750,000 people every year in the United States alone. The Hh and Wg/Wnt pathways are operating in a similar way among organisms as different as Drosophila and human, which means that we can use animal models to study these important pathways.

We have been carrying out systematic genetic screens to identify genes controlling pattern formation and growth of Drosophila adult organs. Toward this end, we have identified many novel components in the Hh , Wg and other signaling pathways. For example, our genetic screen has led to an unexpected and important discovery that the cAMP dependent protein kinase, PKA, plays a pivotal role in regulating Hh signal transduction. We found that PKA controls the proteolytic processing and activity of Cubitus interruptus (Ci), a zinc-finger transcription factor that transduces Hh signal into the nuclei. We have identified another Hh signaling component called Slimb, which belongs to the F-box protein family and is involved in the ubiquitin/proteasome pathway. Currently, we are testing the model in which Slimb acts in conjunction with PKA to regulate the proteolysis of Ci.

Ci forms protein complexes with the kinesin-like protein Costal2 (Cos2), the Ser/Thr kinase Fused (Fu), and the tumor suppressor protein  Su(fu). We found that this complex regulates subcellular localization and proteolytic processing of Ci. We are investigating the biochemical mechanisms by which complex formation regulates different aspects of Ci.

Hh transduces signal by binding to the multi-span transmembrane protein Patched (Ptc), leading to the activation of the seven-transmembrane protein Smoothened (Smo). we discovered that Smo transduces Hh signal by recruiting Cos2/Fu/Ci complexes through its carboxy-terminal tail. We are investigating how Smo/Cos2 complex activates Ci. In addition, we are exploring the mechanism by which Smo is activated by Hh.

We have applied similar genetic, molecular and biochemical approaches to tackle other new components in the Hh and related pathways. For example, we identified a novel component in the Hh pathway named cmn (central missing), which encodes a member of membrane-bound acyltransferase that regulates Hh signaling activity by lipid modification of the Hh protein.

Finally, we are interested in understanding how cell growth and organ size are regulated and how growth and patterning are coordinated. Toward this end, we have identified a number of genes whose loss-of-function results in larger organ size or tumor like growth. We have recently discovered that the Drosophila homolog of MST Ser/Thr kinases functions as a tumor suppressor. We demonstrated that dMST forms a complex with two other tumor suppressors, Sav and Wts, to control organ size by restricting cell proliferation and promoting apoptosis. We are exploring the upstream regulators and downstream effectors of this tumor suppressor complex.

Awards & Honors:

Eugene Mc Dermott Scholar in Biomedical Research, UT Southwestern
Leukemia & Lymphoma Society Scholar Award
Searle Scholars, The Chicago Community Trust

Selected References:

Jiang, J. and Struhl, G. 1995. Protein Kinase A and Hedgehog Signaling in Drosophila Limb Development. Cell 80: 563-572.

Jiang, J. and Struhl, G. 1996. Complementary and mutually exclusive activities of ecapentaplegic and Wingless organize axial patterning during Drosophila leg development. Cell 86: 401-409.

Jiang, J. and Struhl, G. 1998. Regulation of the Hedgehog and Wingless signaling pathways by the F-box/WD40 protein Slimb. Nature 391: 493-496.

Spencer, E., Jiang, J., and Chen, Z.J. 1999. Signal-induced ubiquitination of IkBa by the F-box protein, Slimb/b-TrCP. Genes & Development. 13:284-294.

Wang, G., Wang, B., and Jiang, J. 1999. Protein kinase A antagonizes Hedgehog signaling by regulating both the activator and repressor forms of Cubitus interruptus. Genes & Development. 13:2828-2837.

Wang, G., Amanai, K., Wang, B., and Jiang, J. 2000. Interactions with Costal2 and Suppressor of fused regulates nuclear translocation and activity of Cubitus interruptus. Genes & Development 14: 2893-2905.

Amanai, K. and Jiang, J. (2001). Distinct roles of Central missing and Dispatched in sending the Hedgehog signal. Development 128, 5119-27.

Jia, J., Amanai, K., Wang, W., Tang, J., Wang, B., and Jiang, J. 2002. Shaggy/GSK3 antagonizes Hedgehog signaling by regulating Cubitus interruptus. Nature: advance on line publication, 24 March 2002.

Hyuk Wan Ko, Jin Jiang, and Isaac Edery. 2002. A role for Slimb in the degradation of Drosophila PERIOD protein phosphorylated by DOUBLETIME. Nature 420, 673-678.

Jin Jiang. 2002. Degrading Ci: Who is Cul-pable? Genes & Development 16, 2315-2321.

Correia T, Papayannopoulos V, Panin V, Woronoff P, Jiang J, Vogt TF, Irvine KD. 2003. Molecular genetic analysis of the glycosyltransferase Fringe in Drosophila. Proc Natl Acad Sci 100(11), 6404-9.

Jianhang Jia, Chao Tong, and Jin Jiang . 2003. Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its carboxyl-terminal tail. Genes & Development  17, 2709-2720.

Jianhang Jia, Wensheng Zhang, Bing Wang, Richard Trinko, and Jin Jiang. 2003. The Drosophila Ste20 family kinase dMST functions as a tumor suppressor by restricting cell proliferation and promoting apoptosis. Genes & Development  17, 2514-2519.

Gelin Wang and Jin Jiang. 2004. Multiple Cos2/Ci interactions regulate Ci subcellular localization through microtubule dependent and independent mechanisms. Developmental Biology 268, 493-505.

 Jianhang Jia, Chao Tong, Bing Wang, Liping Luo and Jin Jiang. 2004. Hedgehog Signalling Activity of Smoothened Requires Phosphorylation by Protein Kinase A and Casein Kinase I. Nature 432, 1045-1050.

Wensheng Zhang, Yun Zhao, Chao Tong, Geling Wang, Bing Wang, Jianhang Jia, and Jin Jiang. 2005. Hedgehog-regulated Costal2/kinase complexes control phosphorylation and proteolytic processing of Cubitus interruptus. Developmental Cell, 8, 267-278.

Atish Ganuly, Jin Jiang, and Y. Tony IP. 2005. Wnt8 is a target and an inhibitor of the Dorsal Twist Snail network in the gastrulating Drosophila embryo. Development, 132, 3419-3429
 
Jia, J., Ho, F., Tong, C., Zhang, Q., Wang, G., Wang, B., Amanai, K., and Jiang, J. (2005). Phosphorylation of Cubitus interruptus by Double-time/CKIe and CKIa targets it  for Slimb/b-TRCP mediated proteolytic processing. Dev. Cell  9, 819-830.

Jianhang Jia and Jin Jiang. 2006. Decoding the Hedgehog Signal in Animal Development. Cell and Molecular Life Science, 63 (11), 1249-65.

 Qing Zhang, Lei Zhang, Bing Wang, Chan-Yen Ou, Cheng-Ting Chien, and Jin Jiang. 2006. A Hedgehog-induced BTB protein modulates Hedgehog signaling responses by degrading Ci/Gli transcription factor. Dev. Cell 10, 719-729.

Jin Jiang. 2006. Regulation of Hh/Gli Signaling by Dual Ubiquitin Pathways. Cell Cycle 5 (21), 5 (21) 2457 - 2463.

Chao Tong and Jin Jiang. 2006. Using Immunoprecipitation to Study Protein-protein Interactions in Hedgehog Signaling Pathway, Methods in Molecular Biology 397, 215-229

Lei Zhang, Jianhang Jia, Bing Wang, Kazuhito Amanai, Keith A. Wharton, Jr.1, and Jin Jiang. 2006. Regulation of Wingless signaling by the CKI family in Drosophila limb development. Developmental Biology 299 (1): 221-237.

Chan-Yen Ou, Chien-Hsiang Wang, Jin Jiang, Cheng-Ting Chien. 2007. Suppression of Hedgehog signaling by Cul3 ligases in proliferation control of retinal precursors, Developmental Biology 308(1):106-119

Yajuan Liu, Xuesong Cao, Jin Jiang, and Jianhang Jia. 2007. Fused-Costal2 protein complex regulates Hedgehog-induced Smo phosphorylation and cell-surface accumulation. Genes & Development 21(15):1949-63.

Yun Zhao, Chao Tong, and Jin Jiang. 2007. Hedgehog regulates Smoothened activity by inducing a conformational switch. Nature (article) 450, 252-258.

Yun Zhao, Chao Tong, and Jin Jiang. 2007. Transducing the Hedgehog Signal across the plasma
membrane. Fly 6, 333-336.

Lei Zhang, Fangfang Ren, Qing Zhang, Yongbin Chen, Bing Wang, and Jin Jiang. 2008. The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control. Developmental Cell 14, 377-387.

To access any of the publications referenced on this website please visit http://www.ncbi.nlm.nih.gov/PubMed